1. Field of the Invention
The invention is related to a novel structure for a Ga-68 radionuclide generator that uses two washing solutions to pass through two Ge-68 absorbents to wash out different chemical forms of Ga-68 nuclide.
2. Description of the Prior Art
Because parent nuclide Ge-68 has long half-life, Ge-68/Ga-68 nuclide generator can be used for more than one year to steadily provide Ga-68 nuclide.
In the past, Ge-68 is adsorbed on inorganic materials like silicon dioxide, aluminum oxide or tin oxide to produce Ga-68 nuclide generator. With these materials, there is inevitably inconvenience. For example, if a generator uses aluminum oxide as adsorption column, it will need EDTA (ethylediaminetetraacetic acid) solution to wash out daughter nuclide Ga-68. Since Ga-68-EDTA is a complex with very stable structure, it takes some complicated processes to convert Ga-68 into radiopharmaceuticals. Also because Ga-68 has short half-life, the conversion process will lose some materials. If a generator uses tin oxide as adsorption column, it will need 1N HCl solution or more concentrated to wash out daughter nuclide Ga-68. Thus, Ga-68 nuclide exists as chlorinated Ga and can be used after neutralization. However, the trace amount of inorganic salt can be dissolved and carried out by a strong acid(HC1 concentration >1N) and easily cause metal ion contamination. Its convenience lies in the further labeling for Ga-68 with ligand.
The Ga-68 nuclide generators that are made from adsorption of Ge-68 in silicon dioxide, aluminum oxide or tin oxide have the following common features: (1) existing as a form of strong acid solution (HCl concentration>1N), (2) easily causing ion metal contamination, (3) if the chemical form of Ga-68-gallium citrate is needed, it is more time consuming and is not suitable for pharmaceutical production or clinical use because the exposure of operators to radiation is higher, (4) if Ga-68 nuclide exists as gallium chloride, it cannot be directly used for clinical purpose and needs further labeling for Ga-68 nuclide with ligand.
The Ga-68 nuclide generator that is made from adsorption of Ge-68 in organic resins has the following features: (1) it needs diluted sodium citrate or sodium phosphate solution to wash Ga-68 nuclide, (2) it exists as Ga-68-gallium citrate, (3) it does not cause ion metal contamination, (4) if the chemical form of Ga-68-gallium chloride is needed, it is more time consuming and is not suitable for pharmaceutical production or clinical use because the exposure of operators to radiation is higher.
Ga-68 nuclide has found increasing applications in PET radiopharmaceuticals. Single ion form of Ga-68 nuclide generator is not sufficient to meet the demand of diversified development of Ga-68 applications in radiopharmaceuticals. In review of existing literatures and patents, such as U.S. application Ser. No. 12/745,715, which from Fe (III) conducts purification with automatic apparatus to produce single chemical form of Ga-68 nuclide; or another U.S. publication 60/928,723, which uses washing solution and adsorption column for multiple purification operation to produce single chemical form of Ga-68 nuclide, it is found that there is no example like this invention that adopts a process to combine two different washing solutions and two different adsorption columns to obtain different chemical forms of Ga-68 nuclide, i.e. Ga-68-gallium citrate and Ga-68-gallium chloride.